Clinical Characteristics And Prognosis Of Patients With Drug-induced Liver Injury

BackgroundDrug-induced liver injury(DILI)is one of the common and serious adverse drug reactions,which can lead to acute liver failure and even death in severe cases.According to recent reports,there are more than 1100 known chemical or biological drugs with potential hepatotoxicity.In China,there are a huge population base,a wide variety of clinical drugs,and the prevalence of irregular drug use.Medical personnel and the public have insufficient awareness of drug safety issues and DILI.The prevalence of DILI is also serious and has become a clinical problem that can be ignored.ObjectivesBy investigating the epidemiology,clinical characteristics of drug-induced liver injury,clinical characteristics of drug-related liver failure and risk factors of death,we will identity the common drugs that cause drug-induced liver injury and the main factors that affect the prognosis.The prediction model of death risk was established to guide clinical practice.MethodsThis study investigated the information of hospitalized patients diagnosed with drug-induced liver injury in Shandong Provincial Public Health Clinical Center during 2011.01.01-2020.12.31.According to the 2015 edition of "Guidelines for the Diagnosis and Treatment of Drug-induced Liver Injury",the inclusion and exclusion criteria were formulated,and the medical records were re-screened according to the criteria.And a retrospective study method was used to collect the required patient information in detail,including demography,past history,clinical manifestations,laboratory examination and imaging examination results.This study will analyze the epidemiology,clinical characteristics of drug-induced liver injury,clinical characteristics of drug-related liver failure and risk factors of death.All data were analyzed using SPSS version 25.0 software.The measurement data were expressed as X±S or M(P25,P75).T test or Mann-Whitney U test was used for comparison between groups.Statistical data were presented as example(n)and percentage(%),and)χ2 test was used for comparison between groups.Comparison between multiple groups was performed by one-factor ANOVA or Kruskal-Wallish(K)test.Two-sided test was used,and P<0.05 was considered statistically significant.Risk prediction model for death was established by regression analysis,and goodness of fit and predictive accuracy of model was tested.Results[Epidemiologic feature]803 qualified patients with DILI were included.There were 382 males(47.6%)and 421 females(52.4%),male:female=1:1.1.The average age was 48.38±16.05 years.The most common drugs cause DILI were traditional Chinese herbs in 334 cases(43.4%),followed by antituberculosis drugs in 128 cases(16.6%)and antitumor drugs in 69 cases(9.0%).According to the difference of R value at admission,DILI can be divided into three types:585 cases of hepatocyte type(72.9%),118 cases of mixed type(14.7%)and 100 cases of cholestasis type(12.5%).[Clinical characteristics of drug-related liver failure]803 patients of DILI included 643 patients without basic liver diseases and 160 patients with basic liver diseases.Among 643 patients,there was 44 patients occurred with acute liver failure,and the incidence of acute liver failure was 6.8%.There was no significant difference in the average age between patients with acute liver failure and without acute liver failure(50.52±18.43 vs.47.69±16.48,P=0.10).Patients aged ≥60 years had an increased risk of liver failure(36.4%vs.23.0%,P=0.05).There was no significant difference in the risk of acute liver failure between men and women(P>0.05).The incidence of acute liver failure was significantly increased in patients treated with antituberculosis drugs(34.1%vs.14.7%,P=0.01).Compared with patients without liver failure,the proportion of patients with liver failure with digestive system symptoms,jaundice,fatigue,HE and ascites increased significantly(P<0.05).In patients with ALF,AFP,WBC and N%were elevated(P<0.0.5),while ALB,GGT,CH,TG,HB and PLT were decreased(P>0.05)..24 patients died in acute liver failure with a fatality rate of 54.5%.Among 160 patients with basic liver diseases,there was 32 patients occurred with acute-on-chronic liver failure,and the incidence of acute-on-chronic liver failure was 20.0%.There was no significant difference in the average age between patients with acute-on-chronic liver failure and without acute-on-chronic liver failure(52.28±12.46 vs.49.88±13.60,P=0.71).There was no significant difference in the risk of acute-on-chronic liver failure between men and women(P>0.05).Compared with patients without liver failure,the proportion of patients with acute-on-chronic liver failure with digestive system symptoms,jaundice,fatigue,HE and ascites increased significantly(P<0.05).In patients with acute-on-chronic liver failure,AFP,WBC and N%were elevated(P<0.05),while ALB,GGT,CH,GLU and PLT were decreased(P<0.05).11 patients died in acute-on-chronic liver failure with a fatality rate of 34.3%.[Risk factors for death in patients with DILI]Among 803 patients,37 died,with a case fatality rate of 4.6%(95%CI:3.2%-6.1%).There was no significant difference in the average age between the death group and the survival group(48.00± 16.06 vs.49.70± 15.85,P=0.48).The risk of death in patients treated with antituberculosis drugs increased significantly(P<0.05).There was no significant difference in gender,Chinese herbs,basic liver diseases,antitumor drugs,hypertension,diabetes,cardiovascular diseases,smoking history,drinking history and injury types between the two groups(P>0.05).Compared with the survival group,the patients in the death group were more prone to digestive system symptoms,jaundice,fatigue,HE and ascites.AST,TBIL,WBC level and N%of the dead patients increased significantly(P<0.05),ALB,GGT,CH,TG,GlU,PTA and PLT level decreased significantly(P<0.05).There was no significant difference in ALT,ALP and Hb level between the two groups(P>0.05).Multivariate logistic regression analysis showed that the independent risk factors of death in DILI patients were HE(OR=22.90,95%CI:5.68-92.40),AST>200U/L(OR=6.03,95%CI:1.26-28.75),TB>250μmol/L(OR=13.94,95%CI:2.42-80.31),ALB<30g/L(OR=4.16,95%CI:1.20-14.44),PTA<40%(OR=5.39,95%CI:1.15-25.19).Through the logistic regression equation and combined with the clinical characteristics of DILI,the equation of the death risk prediction model is:P=ea(1+ea),a=-10.50+3.13×HE(0 or 1)+1.80×AST>200U/L(0 or 1)+2.63×TBIL>250μmol/L(0 or 1)+1.43×ALB<30g/L(0 or 1)+1.69 × PTA<40%(0 or 1).(E is an exponential function,and P is the probability of death risk in DILI patients).The goodness of fit of the model was tested,P=0.43.The model works well.Area under ROC curve AUC=0.97,SD=0.01,(P<0.01,95%CI:0.94-0.99).The specificity was 97.3%and the sensitivity was 92.9%.ConclusionsIn our investigation,the main pathogenic drugs of DILI are traditional Chinese medicine,anti-tuberculosis drugs and anti-tumor drugs,which can occur at all ages.The hepatocyte type is the main type of DILI,with good prognosis and low mortality.Patients aged≥60 and nd on antituberculous drugs are more likely to develop acute liver failure.The prediction model of death risk established according to the independent risk factors of death in DILI patients has good fitting and high accuracy,which can be used to guide clinical practice.